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Dynamic Causal Modeling in PTSD and Its Dissociative Subtype: Bottom-Up Versus Top-Down Processing Within Fear and Emotion Regulation Circuitry

Nicholson, AA; Friston, KJ; Zeidman, P; Harricharan, S; McKinnon, MC; Densmore, M; Neufeld, RWJ; ... Lanius, RA; + view all (2017) Dynamic Causal Modeling in PTSD and Its Dissociative Subtype: Bottom-Up Versus Top-Down Processing Within Fear and Emotion Regulation Circuitry. Human Brain Mapping , 38 (11) pp. 5551-5561. 10.1002/hbm.23748. Green open access

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Abstract

Posttraumatic stress disorder (PTSD) is associated with decreased top–down emotion modulation from medial prefrontal cortex (mPFC) regions, a pathophysiology accompanied by hyperarousal and hyperactivation of the amygdala. By contrast, PTSD patients with the dissociative subtype (PTSD + DS) often exhibit increased mPFC top–down modulation and decreased amygdala activation associated with emotional detachment and hypoarousal. Crucially, PTSD and PTSD + DS display distinct functional connectivity within the PFC, amygdala complexes, and the periaqueductal gray (PAG), a region related to defensive responses/emotional coping. However, differences in directed connectivity between these regions have not been established in PTSD, PTSD + DS, or controls. Methods: To examine directed (effective) connectivity among these nodes, as well as group differences, we conducted resting-state stochastic dynamic causal modeling (sDCM) pairwise analyses of coupling between the ventromedial (vm)PFC, the bilateral basolateral and centromedial (CMA) amygdala complexes, and the PAG, in 155 participants (PTSD [n = 62]; PTSD + DS [n = 41]; age-matched healthy trauma-unexposed controls [n = 52]). Results: PTSD was characterized by a pattern of predominant bottom–up connectivity from the amygdala to the vmPFC and from the PAG to the vmPFC and amygdala. Conversely, PTSD + DS exhibited predominant top–down connectivity between all node pairs (from the vmPFC to the amygdala and PAG, and from the amygdala to the PAG). Interestingly, the PTSD + DS group displayed the strongest intrinsic inhibitory connections within the vmPFC. Conclusions: These results suggest the contrasting symptom profiles of PTSD and its dissociative subtype (hyper- vs. hypo-emotionality, respectively) may be driven by complementary changes in directed connectivity corresponding to bottom–up defensive fear processing versus enhanced top–down regulation.

Type: Article
Title: Dynamic Causal Modeling in PTSD and Its Dissociative Subtype: Bottom-Up Versus Top-Down Processing Within Fear and Emotion Regulation Circuitry
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/hbm.23748
Publisher version: https://doi.org/10.1002/hbm.23748
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Science & Technology, Life Sciences & Biomedicine, Neurosciences, Neuroimaging, Radiology, Nuclear Medicine & Medical Imaging, Neurosciences & Neurology, posttraumatic stress disorder, dynamic causal modeling, amygdala, prefrontal cortex, periaqueductal gray, fMRI, connectivity, POSTTRAUMATIC-STRESS-DISORDER, PERIAQUEDUCTAL GRAY, FUNCTIONAL CONNECTIVITY, LEARNED FEAR, LATENT CLASS, AMYGDALA, RESPONSES, NEUROSCIENCE, ANXIETY, THREAT
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Imaging Neuroscience
URI: http://discovery.ucl.ac.uk/id/eprint/10024298
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